A Study of Enzalutamide and LY3023414 in Men With Prostate Cancer

Prostate Cancer Metastatic Clinical Trial

Official title:

A Double-Blinded, Placebo-Controlled, Randomized Phase II Study of Enzalutamide With or Without the PI3 Kinase/mTOR Inhibitor LY3023414 in Men With Metastatic Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02407054
• Other study ID #: 15798
• Secondary ID: I6A-MC-CBBD
• Status: Completed
• Phase: Phase 2
• Start date: April 29, 2015
• Est. completion date: April 16, 2020

Study information

• Verified date: June 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY3023414 in combination with enzalutamide in men with prostate cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: April 16, 2020
• Est. primary completion date: September 26, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate.

• Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan.

• Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2).

• Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Participants must have failed prior abiraterone treatment.

• Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter.

• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

• Ability to swallow the study drugs whole.

• Adequate hematologic function.

• Adequate coagulation parameters, defined as international normalization ratio (INR) = 2.

• Availability of tumor tissue from any time since diagnosis of prostate cancer disease. If no tumor samples are available the participant might still be eligible following discussion between the investigator and the medical monitor.

Exclusion Criteria:

• Prior cytotoxic chemotherapy, immunotherapy, a PI3K/AKT/mTOR agent (including TORC1 and TORC2 inhibitors), or RA 223 dichloride for the treatment of castration resistant prostate cancer (CRPC). Participants may have received docetaxel in the hormone-sensitive setting.

• Prior investigational new generation potent anti-androgen therapy (such as ARN 509).

• Prior treatment with enzalutamide.

• Pathological finding consistent with small cell carcinoma of the prostate.

• Prior systemic treatment with an azole drug (fluconazole, itraconazole) within 4 weeks of cycle 1 day 1.

• Known brain metastasis.

• History of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1.

• Uncontrolled hypertension (systolic blood pressure [BP] = 160 millimeters of mercury [mmHg] or diastolic BP = 95 mmHg).

• Have serious pre-existing medical conditions (at the discretion of the investigator).

• Have known acute or chronic leukemia or current hematologic malignancies that, in the judgment of the investigator and sponsor, may affect the interpretation of results.

• Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c <7%.

• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, grade =2 diarrhea, and malabsorption syndrome).

• Have a history of New York Heart Association (NYHA) Class =3, QTc interval > 480 milliseconds (ms) on screening electrocardiogram (ECG) per Friderica's formula, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration.

• Clinically significant electrolyte imbalance = grade 2.

• Currently receiving treatment with therapeutic doses of warfarin sodium.

• Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) =28 days prior to day 1 of cycle 1.

• Concurrent serious infections requiring parenteral antibiotic therapy.

• Have a second primary malignancy that in the judgment of the investigator and medical monitor may affect the interpretation of results.

• Have an active, known fungal, bacterial, and/or known viral infection.

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• LY3023414
Administered orally
• Enzalutamide
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Southwestern Medical Center - Dallas	Dallas	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Fort Wayne Oncology & Hematology	Fort Wayne	Indiana
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Fort Worth	Texas
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Urology Centers of Alabama, P.C.	Homewood	Alabama
United States	Texas Oncology-Memorial City	Houston	Texas
United States	Indiana Cancer Pavilion	Indianapolis	Indiana
United States	Urological Associates of Lancaster	Lancaster	Pennsylvania
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Prostate Oncology Specialists	Marina Del Rey	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Minnesota Oncology/Hematology PA	Minneapolis	Minnesota
United States	Garden State Urology	Morristown	New Jersey
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Urology Associates	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Urology Cancer Center	Omaha	Nebraska
United States	Univ of Pittsburgh Cancer Inst. (UPCI)	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	Sharp Memorial Hospital	San Diego	California
United States	Swedish Medical Center	Seattle	Washington
United States	Oregon Urology Institute	Springfield	Oregon
United States	Associated Medical Professionals of NY	Syracuse	New York
United States	US Oncology	The Woodlands	Texas
United States	Northwest Cancer Specialists PC	Tualatin	Oregon
United States	Delaware Valley Urology	Voorhees	New Jersey
United States	Florida Cancer Specialists East	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Sarah Cannon Development Innovations

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part B: Progression Free Survival (PFS)	PFS was defined as the time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2) or death by any cause regardless of whether the participants withdraws from study drug or receives a subsequent anti-cancer therapy (as determined by the investigator). Participants who have not progressed or died at the time of assessment were censored at the time of the last date of assessment (tumor evaluation or PSA level).	Randomization to Measured Progressive Disease or Death from Any Cause (Up To 34 Months)
Secondary	Part B: Time to Disease Progression (TTP)	TTP was defined as time from randomization until the date of clinical (symptomatic or radiographic) and/or prostate specific antigen (PSA) disease progression per Prostate Cancer Clinical Trials Working Group (PCWG2).	Randomization to Objective Disease Progression (Up To 34 Months)
Secondary	Part B: Percentage of Participants With Prostate Specific Antigen Response	PSA response was defined as more than 50% and 90% reduction from baseline to lowest post baseline value. 95% Confidence Intervals are based on Fisher's Exact Method.	12 Weeks
Secondary	Part A: Pharmacokinetic (PK): Area Under the Concentration-time Curve Over the Dosing Interval (AUCt) of LY3023414	PK: Area under the Concentration-time Curve Over the Dosing Interval (AUCt) of LY3023414; Time Frame: Part A LY3023414 200 mg: Day-1 pre-dose, 1.5, 3, and 6 hours post LY3023414 dose, Cycle 1 Day 1 pre-dose of LY3023414 and enzalutamide, and Part A Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose;	Part A: 200 mg LY3023414 + 160 mg Enzalutamide: Cycle 1 Day 15 Pre-dose of LY3023414 and enzalutamide 1.5, 3, and 6 hours post LY3023414 dose
Secondary	Part B: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions.	Randomization to Second Measured Complete Response or Partial Response (Up To 34 Months)

External Links

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